Patterned laser treatment

ABSTRACT

Patterned laser treatment of the retina is provided. A visible alignment pattern having at least two separated spots is projected onto the retina. By triggering a laser subsystem, doses of laser energy are automatically provided to at least two treatment locations coincident with the alignment spots. All of the doses of laser energy may be delivered in less than about 1 second, which is a typical eye fixation time. A scanner can be used to sequentially move an alignment beam from spot to spot on the retina and to move a treatment laser beam from location to location on the retina.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. Ser. No. 10/745,954, filed onDec. 24, 2003 now U.S. Pat. No. 7,766,903, entitled “Patterned LaserTreatment of the Retina”, and hereby incorporated by reference in itsentirety.

FIELD OF THE INVENTION

The present invention relates to laser treatment of the retina, and moreparticularly to laser treatment of the retina at multiple locations.

BACKGROUND

Several retinal conditions, such as proliferative diabetic retinopathy,diabetic macular edema, and retinal venous occlusive diseases, respondwell to retinal photocoagulation treatment. In fact, panretinalphotocoagulation (PRP) is the current standard of care for proliferativediabetic retinopathy. Retinal photocoagulation procedures frequentlyrequire delivery of a large number of laser doses to the retina. Forexample, PRP typically requires laser treatment of at least 1500locations. Retinal photocoagulation is typically performedpoint-by-point, where each individual dose is positioned and deliveredby the physician. Typically, laser spots range from 50-500 microns indiameter, have pulse durations of 100-200 ms and have a beam power of200-800 mW. Laser wavelengths are typically green, yellow or red,although occasionally infrared radiation is used. Point by pointtreatment of a large number of locations tends to be a lengthyprocedure, which frequently results in physician fatigue and patientdiscomfort.

Various approaches for reducing retinal photocoagulation treatment timehave been developed. Some approaches are based on taking an image of theretina to be treated, planning and aligning all treatment locations withreference to the retinal image, and treating all of these locationsautomatically. A tracking system is usually required in these approachesto ensure alignment between planned treatment locations defined on theimage and actual treatment locations on the retina. Such trackingsystems must process large amounts of data in real time, and thereforetend to be complex and difficult to implement. A representativediscussion of such an approach is found in Wright et al., Journal ofBiomedical Optics, 5(1), 56-61, January 2000.

Other approaches provide multiple treatment laser beams to reducetreatment time. Multiple treatment beams can be provided by an opticalbeam-multiplier (e.g., U.S. Pat. No. 4,884,884 to Reis) or by an opticalfiber having multiple closely spaced outputs (e.g., U.S. Pat. No.5,921,981 to Bahmanyar et al.). Although these approaches are lesscomplex than approaches based on retinal imaging and tracking, thetreatment beam configurations cannot be easily or flexibly adjusted. Forexample, Reis discusses provision of a turret changer to permitselection of one beam multiplier from a set of several different beammultipliers. Such selection of one beam multiplier from a handful ofbeam multipliers is unlikely to provide the degree of flexibilitydesired in practice. Accordingly, there is a need for simple andflexible multi-location retina treatment that is not provided by knownmethods.

SUMMARY

It is an object of the invention to provide flexible multi-locationretina treatment without the complexity of retinal image tracking. Thepresent invention provides a system and method for patterned lasertreatment of the retina. A visible alignment pattern having at least twoseparated spots is projected onto the retina. By triggering a lasersubsystem, doses of laser energy are automatically provided to at leasttwo treatment locations coincident with the alignment spots. Preferably,all of the doses of laser energy are delivered in less than about 1second, which is a typical eye fixation time. In a preferred embodiment,a scanner is used to sequentially move an alignment beam from spot tospot on the retina and to move a treatment laser beam from location tolocation on the retina.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flow diagram of a method of the present invention.

FIG. 2 shows a block diagram of an apparatus of the present inventionproviding an alignment pattern and treatment locations to a retina.

FIGS. 3 a and 3 b are in vivo photographs showing an alignment patternand treatment locations respectively in an animal subject.

FIG. 4 shows an apparatus of an embodiment of the present invention.

FIG. 5 is a fundus photograph comparing treatment results provided by amethod of the present invention with treatment results provided by aconventional point-by-point method, in a human subject.

FIGS. 6 a-6 h show examples of predefined patterns suitable for use withthe invention.

FIG. 7 shows several closely spaced fixation spots making up a fixationpattern, where the fixation pattern is not seen as circular by apatient.

FIG. 8 shows an apparatus of an alternate embodiment of the inventionhaving adjustment optics for changing the size of alignment andtreatment beams on the retina.

FIG. 9 shows an apparatus of an alternate embodiment of the inventionhaving a dual-output coupling fiber.

FIG. 10 shows a database suitable for recording images of alignmentpatterns and treatment locations according to an embodiment of theinvention.

DETAILED DESCRIPTION

FIG. 1 is a flow diagram of a method of the present invention. A firststep 10 of this method is projecting a visible alignment pattern havingat least two separated spots onto a retina. In most cases, although notabsolutely required to practice the invention, step 12 of adjusting thealignment pattern is performed next by an operator (e.g. a physician ora technician). This adjustment can include translation of the alignmentpattern relative to the retina, in order to select areas to treat and/orto ensure that critical parts of the retina (e.g., the fovea or majorblood vessels) are not treated with laser radiation. Adjustment of thepattern can also include rotation and/or scaling of the pattern, and/orchanging the size of the spots to be treated.

Step 14 of triggering a laser subsystem is performed by an operator(e.g., by pressing a foot switch, pressing button, giving an audiocommand etc.). After step 14, step 16 is automatically performed, whichentails delivering laser doses to locations on the retina which arealigned to some (or all) of the alignment pattern spots. Preferably, allof the laser doses are delivered in less than about 1 second, since 1second is a typical eye fixation time. In this manner, doses of laserenergy can be delivered to multiple locations on the retina which arealigned with spots in the alignment pattern, responsive to a singleoperator action. Thus, this method provides reduced treatment time forphotocoagulation procedures. By delivering all the doses of laser energyin a time less than an eye fixation time, the requirement for retinaltracking is eliminated, since the eye can be expected to remainmotionless during treatment. Thus, this method does not require thecomplexity of retinal image tracking.

An upper limit to the number of locations which can be treated in asingle automatic application (or session or sequence) is obtained bydividing the maximum total treatment time by the pulse duration at eachtreatment location. For example, for 100 ms pulses and a maximum totaltreatment time of 1 second, the maximum number of treatment locations is10. We have found that 10-50 ms pulses are preferable for practicing theinvention, and 10-30 ms pulses are more preferred. The correspondingrange of maximum number of locations treated in 1 second for the morepreferred pulse duration range is 33-100, which is enough to provide asignificant reduction in total treatment time. For example, 1500locations can be treated using only 30 automatic applications ofapproximately 1 second each when each application treats 50 locationswith an individual pulse duration of 20 ms.

FIG. 2 shows a block diagram of a system 20 suitable for performing themethod of FIG. 1, as well as a retina 23 having an alignment pattern andtreatment locations on it. Within system 20 are two subsystems, analignment subsystem 21 and a laser subsystem 22. Alignment subsystem 21provides a visible alignment pattern having at least two spots to retina23. In the example of FIG. 2, the alignment pattern has spots 24arranged in a circle and a spot 26 at or near the center of the circleformed by spots 24. Alignment pattern spots are shown with dotted lineson FIG. 2. Laser subsystem 22 provides doses of laser energy to at leasttwo treatment locations on retina 23 which are substantially alignedwith alignment pattern spots. In the example of FIG. 2, treatmentlocations 25 are arranged in a circle and are substantially aligned withalignment spots 24. Treatment locations are shown with solid lines onFIG. 2. Perfect alignment of alignment spots to treatment locations isnot required. For example, FIG. 2 shows treatment locations 25 which areslightly smaller than alignment spots 24. Alternatively, treatmentlocations 25 could be larger than alignment spots 24 and/or be slightlyoffset from alignment spots 24. There is no treatment locationcorresponding to spot 26. Therefore, spot 26 can be used as a fixationspot, for example, by aligning it to a patient's fovea and requestingthe patient to fixate on spot 26.

In the example of FIG. 2, the alignment pattern has an exclusion zone 27within which no treatment locations are disposed. Such an exclusion zoneis helpful for ensuring that locations on the retina which should not belaser treated are not laser treated. For example, the exclusion zone canbe aligned with the fovea so that the fovea is not treated. Theexclusion zone may or may not contain alignment pattern spots. If analignment pattern spot is present within the exclusion zone, it can beused to aid alignment of the exclusion zone by being used as a fixationspot as indicated above, or it can be aligned to a particular feature,such as a retinal tear, which should not be treated.

FIGS. 3 a and 3 b are photographs of an alignment pattern and treatmentlocations respectively from an animal test of a method according to theinvention. The test shown in FIGS. 3 a and 3 b corresponds to thealignment pattern and treatment locations shown in FIG. 2. Inparticular, there is no treatment location in FIG. 3 b corresponding tothe central alignment spot on FIG. 3 a.

FIG. 4 shows an apparatus of an embodiment of the present invention. Asource module 410 is coupled by a fiber 420 to a scanner module 430.Source module 410 and scanner module 430 are controlled by a processor440. Radiation emitted from scanner module 430 impinges on a retina 470of an eye 460, and typically passes through an optional contact lens 450on the way.

In the example of FIG. 4, source module 410 includes an alignment source411 and a separate laser source 413, which is a preferred embodiment,since it increases flexibility. For example, alignment source 411 canhave a wavelength selected within the visible spectrum to provideimproved visibility of the alignment pattern on the retina, while lasersource 413 can have a wavelength selected to provide improved treatmentresults. In fact, the wavelength of laser source 413 can be at anon-visible wavelength. Alignment source 411 can be an LED (LightEmitting Diode) source or a low power laser source providing less than 1mW per alignment spot. Laser source 413 can be an Argon laser, Kryptonlaser, diode laser, Nd-YAG laser or any other pulsed or continuous wavelaser suitable for retinal therapy. Typically, the output power of lasersource 413 is from about 200 mW to about 2 W.

Laser source 413 can be a pulsed laser, which can be suitable forapplications such as selective Retinal Pigment Epithelial (RPE)treatment. In this case the laser pulse duration is typically within arange of about 20 ns to 2 μs, and the laser pulse energy density iswithin a range of about 50 to 500 mJ/cm². The short laser pulses can beapplied to each treatment location in a burst. The repetition rate ofpulses in the burst can be selected by dividing the desired number ofpulses by the duration of treatment in each location. For example,delivery of 50 pulses during 30 ms is provided by a repetition rate of1.7 kHz.

An alignment shutter 412 and a laser shutter 414 are disposed in thebeam paths of alignment source 411 and laser source 413 respectively.These shutters provide rapid on-off switching of the alignment and laserbeams under the control of processor 440 to define the pulse duration oflaser energy doses. As indicated above, we have found that 10-50 mspulses are preferable for practicing the invention for coagulationapplications, and 10-30 ms pulses are more preferred. Approaches forimplementing shutters 412 and 414 include, but are not limited to,mechanical shutters, liquid crystal display (LCD) devices, and/oracousto-optic modulators (AOMs). Alternatively, shutters 412 and/or 414can be omitted if sources 411 and/or 413 provide rapid on-off switchingcapability. In the example of FIG. 4, the laser and alignment beams arecombined by a turning mirror 415 and a dichroic beamsplitter 416, andthen coupled into fiber 420 by coupling optics 417. Of course, manyother arrangements of optical components are also suitable for couplingsources 411 and 413 into fiber 420, and can be used to practice theinvention.

Optical fiber 420 is preferably a highly multimode fiber (i.e., numberof modes>20) at the wavelength of laser source 413 and at the wavelengthof alignment source 411. A highly multimode optical fiber provides asmooth and nearly constant optical intensity distribution at its output,which is desirable for practicing the invention.

Laser and alignment light emitted from fiber 420 is received by scannermodule 430. Within scanner module 430, light emitted from fiber 420 iscollimated by coupling optics 431, and is then deflected by scanningelements 432 and 433. In the example of FIG. 4, scanning elements 432and 433 each provide 1-D beam deflection, so two such elements are usedto provide 2-D beam deflection. Scanning elements 432 and 433 arepreferably galvanically or piezoelectrically actuated optical elementssuitable for beam deflection, such as mirrors. Of course, otherdeflection elements and/or actuation methods can also be used topractice the invention. Deflected beams 437 pass through lens 434 andoptional contact lens 450 before reaching retina 470 of eye 460. Lens434 and optional lens 450, in combination with refractive elements ofeye 460 such as its cornea and lens, provide a selected alignment andlaser beam spot size at retina 470, which is typically in a range ofabout 50 to 500 microns.

In operation of the embodiment of FIG. 4, scanning elements 432 and 433and shutters 412 and 414 are used to define an alignment pattern and aset of treatment locations on retina 470. For example, to create thealignment pattern shown on FIG. 2, scanning elements 432 and 433 aredriven such that an alignment beam from alignment source 411 defines apattern having spots 24 and spot 26 on retina 470. Shutter 412 is closedwhile this beam is moved from spot to spot. The treatment locationsshown on FIG. 2 are then provided by opening shutter 414 when thealignment beam is aligned with one of spots 24, and closing shutter 414while the alignment beam is moved from spot to spot, and while thealignment beam is aligned with fixation spot 26.

An optional retina imager 436 is preferably included in a systemaccording to the invention, to allow the physician to observe thealignment patterns and/or treatment locations on retina 470. In theexample of FIG. 4, retina imager 436 is optically coupled to retina 470via a partially transmissive mirror 435. Partially transmissive mirror435 is preferably highly reflective at the wavelength of laser source413, partially reflective and partially transmissive at the wavelengthof alignment source 411, and transmissive at wavelength(s) of anyillumination source that may be present within retina imager 436. Ofcourse, other methods of coupling retina imager 436 to retina 470 whilepermitting deflected laser and alignment beams 437 to also reach retina470 can also be used to practice the invention.

Retina imager 436 can be a biomicroscope or slit lamp, or any otherinstrument for observing the retina. In some cases, the physician willlook into an eyepiece of retina imager 436 to observe retina 470. Inother cases, retina imager 436 will include a video display of retina470 to make observation of retina 470 more convenient. In the preferredembodiment where alignment source 411 and laser source 413 havedifferent wavelengths, retina imager 436 will typically include anoptical wavelength selective filter at its input to block light havingthe wavelength of laser source 413 from entering retina imager 436,while permitting light having the wavelength of alignment source 411 toenter retina imager 436. Such a filter is particularly important whenobservations are performed directly by a physician.

Retina imager 436 can provide either a normal image or an invertedimage, depending on its optical design. Typical simple optical imagingdesigns provide inverted images, and addition of an optical imageinverter to such a design will provide a normal (or non-inverted image).In some cases, it is preferable for the images provided by retina imager436 to be normal images, and in such cases, an optical image invertercan be included within retina imager 436.

Many optical elements of the embodiment of FIG. 4 belong to both thealignment subsystem (21 on FIG. 2) and to the laser subsystem (22 onFIG. 2). This commonality between the two subsystems providesco-alignment of the laser and alignment beams. In particular, fiber 420and scanning elements 432 and 433 are common to both subsystems. Thisgreatly simplifies the embodiment of FIG. 4 compared to an embodimentwhere both sources are not coupled into the same fiber, or wheredeflection of the alignment and laser beams is performed with twoseparate scanners. The flexibility of the embodiment of FIG. 4 resultsmainly from having two sources 411 and 413 with two independent shutters412 and 414 respectively. The embodiment of FIG. 4 shows a preferred wayof aligning the laser treatment locations to the alignment spots, namelycoupling both alignment source 411 and laser source 413 into the sameoptical fiber 420. Other methods of co-aligning alignment subsystem 21and laser subsystem 22 can also be used to practice the invention.

FIG. 5 is a photograph of retinal coagulation treatment results in ahuman. Treatment locations 52 were treated according to the presentinvention, while treatment locations 54 were treated with a conventionalpoint-by-point technique. Clearly, treatment locations 52 are much moreuniform in appearance and spacing than treatment locations 54, whichdemonstrates one of the principal advantages of the present invention.The photograph of FIG. 5 is a typical result from a test of a prototypeof the invention on 9 patients with diabetic retinopathy. In this test,treatment time was reduced by a factor of 2.5 to 7.8. The level of painexperienced by the patients was also significantly reduced compared toconventional therapy.

Processor 440 on FIG. 4 controls source module 410 and scanner module430. More particularly, processor 440 controls scanning elements 432 and433, and shutters 412 and 414, to define the alignment pattern andtreatment locations on retina 470. Since the alignment pattern andtreatment locations are under computer control, a great deal offlexibility is provided. For example, as indicated in the discussion ofFIG. 2, an alignment spot can be an untreated spot having nocorresponding treatment location, which can be of benefit when planninggrid photocoagulation of the macula or treatment of a peripheral tear ofthe retina. Such an untreated spot can also be used as a fixation spotto reduce eye motion.

The flexibility provided by the present invention can also be exploitedby creating a set of predefined alignment patterns. A physician canselect one or more of these predefined patterns, and adjust theorientation and/or scale of the pattern (i.e., rotate and/ormagnify/demagnify the pattern), and/or translate the pattern relative tothe retina, and/or change the number and/or size of the spots in thepattern, until it is appropriately aligned to a patient's retina. Thusan alignment pattern having a large number of spots in it can be alignedto a patient's retina without the physician having to deal with eachalignment spot individually. A graphical user interface is a preferredapproach for manipulating alignment patterns, including predefinedalignment patterns. A graphical user interface is particularlyconvenient when used in combination with a retina imager 436 including avideo display. FIGS. 6 a-6 h show examples of suitable predefinedpatterns for practicing the invention, although the invention can bepracticed with any pattern. FIGS. 6 a, 6 b, 6 d, 6 d, 6 e, 6 f and 6 gshow a circular pattern, elliptical pattern, donut pattern, quadrantpattern, rectangular pattern, arc pattern and annular arc patternrespectively. Furthermore, a user-defined pattern can be created andstored for later use, and such a user-defined pattern can be used in thesame way as any other predefined pattern. A database, such as describedabove, can be used to store user-defined patterns.

FIG. 6 h shows an example of how such predefined patterns can be used inpractice. In the example of FIG. 6 h, feature 61 is a retinal feature,such as the macula, or a retinal tear, or a localized region of latticedegeneration, which should not be laser treated, but which should besurrounded by laser treated regions. In the case of smaller regions tobe treated with a relatively limited number of total spots, typicallyless than 100, the entire predefined treatment pattern can be applied inless than one second. Alternatively, another method for laser treatmentis to first laser treat according to a predefined circular pattern 62encircling feature 61, and then fill in the treatment area outsidecircular pattern 62 using annular arc patterns 63, 64, 65, and 66. Suchannular arc patterns preferably have adjustable size and orientation.The four orientations required to form a complete ring, as shown on FIG.6 h, are preferably predefined. Furthermore, the spot pattern of suchannular arcs is preferably user-selectable. For example, FIG. 6 h showsannular arc patterns having a 3×8 spot pattern. Other spot patterns,such as 4×6, 5×5, 6×6, 6×8, and 7×7 are also suitable for such annulararc patterns. User selection of annular arc pattern size, orientationand spot pattern is preferably accomplished with a graphical userinterface, as indicated above.

A further example of the flexibility provided by the current inventionis shown in FIG. 7, where several untreated alignment spots 710 arepositioned next to each other to define a shape which is non-circular.In the example of FIG. 7, this shape is a + sign. When alignment spots710 on FIG. 7 are used as fixation spots, the patient will perceive anon-circular shape, which can aid the patient in fixating on theintended fixation spot as opposed to some other spot in the alignmentpattern. An alternative approach for distinguishing an untreatedfixation spot from a non-fixation spot that will be treated is to scanthe alignment pattern such that the fixation spot is perceived asblinking while non-fixation spots are perceived as steady (or viceversa).

Still another way to provide flexibility in the present invention isshown in the embodiment of FIG. 8, which differs from the embodiment ofFIG. 4 only by insertion of adjustment optics 810 into the beam pathswithin scanning module 430. Adjustment optics 810, which can be anelectronically controllable zoom lens, allows the spot size of thealignment and laser beams on retina 470 to be adjusted.

In the embodiments of FIGS. 4 and 8, doses of laser energy are providedto the treatment locations sequentially. In some cases, it can bebeneficial to provide doses of laser energy to treatment locationssimultaneously. For example, the embodiment of FIG. 9 differs from theembodiment of FIG. 4 only by substitution of dual output fiber 910 foroptical fiber 420 on FIG. 4. Dual output fiber 910 defines two closelyspaced spots, and this pattern of two closely spaced spots can bepositioned to various positions on retina 470 by scanning elements 432and 433, as shown on FIG. 9. A benefit of this approach is that roughlytwice as many spots can be treated in a given amount of time, since twodoses are always provided simultaneously as opposed to only a singledose being provided at any one time. However, this approach is lessflexible than scanning a single spot. For example, it is not possible totreat only one spot of a pair of spots defined by fiber 910. Also, thepower from laser source 413 is split among all doses which aresimultaneously delivered, so simultaneous delivery of a large number ofdoses will require much more power from laser source 413.

In clinical use, it will typically be preferred to include recordkeepingin a system according to the invention. As shown on FIG. 10, a database1010 can be used to store observed images obtained from retina imager436 of system 20. Database 1010 includes multiple records 1020, andrecords 1020 can include information such as images 1030 of alignmentpatterns, images 1040 of treatment locations, and/or patient information1050. Images 1040 and 1050 are preferably stored in a digital format forease of handling and access.

What is claimed is:
 1. A method for laser treatment of tissue of apatient, the method comprising: displaying a visible alignment patternthat defines a plurality of separate treatment locations on the tissue;and triggering a laser subsystem with an operator action to deliversequential doses of laser energy to at least two of the treatmentlocations defined by the alignment pattern within a time period of about1 second.
 2. The method of claim 1, wherein the laser subsystemcomprises a laser source, and wherein the alignment pattern is providedby an alignment source other than the laser source.
 3. The method ofclaim 2, wherein the laser energy is at a non-visible wavelength.
 4. Themethod of claim 2, further comprising guiding light from the lasersource toward the tissue with an optical fiber, and guiding light fromthe alignment source toward the tissue with the optical fiber.
 5. Themethod of claim 1, wherein the tissue is a retina of an eye of thepatient, and further comprising observing the retina with a retinaimager.
 6. The method of claim 5, wherein the retina imager includes abiomicroscope, a slit lamp, a video display or an optical imageinverter.
 7. The method of claim 5, further comprising recordingobservations obtained from the retinal imager in a database.
 8. Themethod of claim 1, wherein the alignment pattern is a predefinedalignment pattern.
 9. The method of claim 8, wherein the predefinedalignment pattern is a quadrant pattern, a circular pattern, anelliptical pattern, a donut pattern, a rectangular pattern, an arcpattern, an annular arc pattern, or a user-defined pattern.
 10. Themethod of claim 8, further comprising adjusting a scale and anorientation of the predefined alignment pattern.
 11. The method of claim1, wherein the alignment pattern further comprises an exclusion zone,within which none of the treatment locations are disposed.
 12. Themethod of claim 11, wherein the tissue is a retina of an eye of thepatient, and further comprising aligning the exclusion zone to the foveaof the retina.
 13. The method of claim 11, wherein the tissue is aretina of an eye of the patient, and further comprising aligning theexclusion zone to a tear within the retina.
 14. The method of claim 1,wherein the tissue is a retina of an eye of the patient, and wherein thealignment pattern further comprises a fixation spot which is not alignedwith any of the treatment locations.
 15. The method of claim 14, furthercomprising aligning the fixation spot to the fovea of the retina. 16.The method of claim 14, wherein the fixation spot is blinking.
 17. Themethod of claim 1, wherein the tissue is a retina of an eye of thepatient, and wherein the alignment pattern further comprises a pluralityof fixation spots which are not aligned with any of the treatmentlocations, and wherein the plurality of fixation spots is other thancircular.
 18. The method of claim 1, further comprising: moving a laserbeam from one of the treatment locations to another of the treatmentlocations with a scanner; and moving an alignment beam from one of thetreatment locations to another of the treatment locations with thescanner to provide the alignment pattern.
 19. The method of claim 18,wherein the scanner comprises a galvanically or piezoelectricallyactuated optical element.
 20. The method of claim 18, further comprisingblocking the laser beam with a laser shutter during the moving a laserbeam.
 21. The method of claim 18, further comprising blocking thealignment beam with an alignment shutter during the moving an alignmentbeam.
 22. The method of claim 1, further comprising altering a size ofthe laser beam with adjustment optics.
 23. The method of claim 1,wherein the alignment pattern comprises spots disposed at the treatmentlocations.